The purpose of this research study is to determine the safety and activity of regorafenib in participants with advanced gastrointestinal stromal tumor (GIST) if the standard approved therapies, imatinib and sunitinib, have failed to control the disease. Regorafenib is a drug that blocks abnormally active signaling enzymes called "tyrosine kinases" which are important to the growth of GIST. This "tyrosine kinase inhibition" is similar to the way that both imatinib and sunitinib work; however, regorafenib blocks certain additional signaling pathways that are not blocked by imatinib or sunitinib. Regorafenib has been not been tested in GIST participants before this research study.

A Multi-center Phase II Study Evaluating the Efficacy and Safety of Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor (GIST), Resistent or Intolerant to at Least Imatinib and Sunitinib

Clinical Benefit as Defined by the Composite of Complete Response, Partial Response and Stable Disease Lasting 16 Weeks or More Per RECIST 1.1 as a Measure of Disease Control [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The composite of complete response, partial response, and stable disease lasting 16 weeks or more per RECIST 1.1 as a measure of disease control. This is for target lesions. Complete response is disappearance of all target lesions and partial response is >+30% decrease in the sum of the longest diameter of target lesions. Stable disease is neither shrinkage by greater than or equal to 30% of the sum of the longest diameter of target lesions or the increase of lesions by greater than or equal to 20% of the sum of the longest diameter of target lesions. Progressive disease is considered an increase of the sum of the longest diameter of target lesions by greater than or equal to 20%.

Secondary Outcome Measures:

Progression-free Survival (PFS) [ Time Frame: From date of enrollment until date of first documented progression or date of death from any cause, whichever came first ] [ Designated as safety issue: No ]

Progression-free survival is defined as the duration of time from start of study drug administration to time of objective disease progression or death due to any cause, whichever comes first. Progression is evaluated every 8 weeks using Response Criteria for Solid Tumors (RECIST) 1.1. Objective disease progression is defined as a 20% increase in the sum of the longest diameter of target lesion(s).

Regorafenib adminstered orally, 160 mg per day on days 1 through 21 of a 28 day cycle

Drug: regorafenib

Taken orally, once a day in the morning for 3 weeks followed by a one week rest period

Other Name: Stivarga

Detailed Description:

In this research study, each planned "cycle" of the study lasts 4 weeks. In the first cycle, participants will come to the clinic on Days 1, 15 and 16. For cycles 2 through 4, they will come to the clinic on Days 1 and 15 of each cycle. For cycle 5 and beyond, they will come to the clinic on Day 1 of each cycle. Repeat tumor imaging will be performed at the end of every 2 cycles during study drug administration (e.g. end of cycles 2, 4, 6, etc.)

During each cycle, participants will take regorafenib by mouth, once a day in the morning, for 3 weeks followed by one week during which you do not take regorafenib (the "rest period").

FDG-PET/CT (Positron Emission Tomography) scans are required as part of this study to monitor effects of the study drug on the participant's GIST. The first scan will take place before the first dose of study drug. If the first scan shows that the "tracer sugar" collection is increased in the participant's GIST, they will have up to 5 additional scans performed at different time points throughout their participation in this research study.

Participants may continue to participate in this research study for as long as they do not have serious side effects or their disease does not get worse.

Measurable disease per RECIST 1.1. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion.

ECOG Performance Status 0 or 1

Adequate organ and marrow function as outlined in the protocol

Fully recovered from the acute effects of prior cancer therapy before initiation of study drug

Patients must be suitable for oral drug administration

Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug

Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration

Exclusion Criteria:

Use of any unapproved tyrosine kinase inhibitors or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study drug

Participants who have had radiotherapy within 4 weeks prior to study entry

Major surgery, or significant traumatic injury within 4 weeks prior to study entry

Presence of symptomatic or uncontrolled brain or central nervous system metastases

Prior exposure to sorafenib

Prior exposure to regorafenib

Known or suspected allergy to the investigational agent or any agent given in association with this trial

Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy or other primary malignancy is neither currently clinically significant nor requiring active intervention

History of clinically significant cardiac disease or congestive heart failure > NYHA class 2. Patients must not have unstable angina or new-onset angina within the last 3 months or myocardial infarction within the past 6 months

Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication

Ongoing infection of Grade 3 or higher

Patients with evidence of, or history of, bleeding diathesis. Any major hemorrhage or bleeding event of Grade 3 or higher within 4 weeks of start of study medication

Non-healing wound, ulcer or bone fracture

Renal failure requiring hemo-or peritoneal dialysis

Dehydration of Grade 2 or greater

Persistent proteinuria Grade 3 or higher

Known history of HIV infection or chronic hepatitis B or C

Uncontrolled intercurrent illness

Pregnant or lactating females

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01068769